In this application for a Core Support Center, we propose to apply the technologies of functional genomics to the study of hepatitis C virus (HCV)-associated liver disease, a public health problem that is a direct consequence of drug abuse and addiction. This center will be composed of a diverse group of NIH-funded investigators, including experts in viral hepatitis, liver disease and transplantation, global gene expression analysis, proteomics, and advanced information technologies. The unifying theme is the desire to gain a detailed understanding of the molecular mechanisms underlying the progression from chronic HCV infection to end-stage liver disease, including cirrhosis and hepatocellular carcinoma. The University of Washington provides an exceptional environment that has fostered a high level of expertise in all these venues, and it is only through a Core Support Center that such a multidisciplinary group of researchers can be brought together to focus their expertise on a single problem. The proposed center will consist of four cores: Microarray & Virology, Proteomics & Modeling, Bioinformatics & Biostatistics, and Administration. Investigators from basic and clinical science will participate in the Microarray & Virology Core, providing a primary human hepatocyte cell culture system and access to unique patient populations, including biopsy material from patients with recurrent HCV after liver transplantation, and from patients co-infected with HCV and human immunodeficiency virus. An established infrastructure is in place for microarray analysis, including extensive experience in gene expression analysis during virus infection. The Proteomics & Modeling core will be located at the Institute for Systems Biology, one of the world's leading proteomics centers. Specialists in computational biology, bioinformatics, and statistics will provide the essential functions of data management, analysis, and statistical evaluation. This group will also develop a national database resource of gene expression and proteomics data that can be accessed via the World Wide Web. This multidisciplinary approach provides a unique opportunity to advance our understanding of viral hepatitis and liver disease to a level far in excess of that which could be obtained by any of these investigators working individually. The Core Support Center provides the mechanism to bring this outstanding group of scientists together and to attract additional scientists of the highest quality.